1-(5-alkylsulfonyl-2-furyl)-2-amido- 1, 3-propanediols and preparation of same



United States Patent 1-(5-ALKYLSULFONYL 2 FURYL)-2-AMIDO 1,3-PROPANEDIOLS AND PREPARATION OF SAME Algird Kreuchunas, Wilmington,Del., assignor to E. I. du Pont de Nemours and Company, Wilmington,Del., a corporation of Delaware No Drawing. Application September 12,1952, Serial No. 309,370

8 Claims. (Cl. 260-3412) This invention relates tol-(-alleylsulfonyl-2-furyl)-2- amido-l,3-propanediols and to a methodfor their preparation.

The 1 (5-alkylsulfonyl-2-furyl)-2-amino-l,3-propanediols of myinventionconform to the formula l-(5-methylsulfonyl 2 furyl)2-(alpha,alphadichloro acetamido) -1,3-propanediol 1-(5 ethylsulfonyl 2furyl) 2-(alpha,alphadichloroacetamido l ,3-propanediol1-(5-n-propylsulfonyl-2-furyl) 2 (alpha,alphadichloro acetamido) -l,3-propanediol 1-(5-isopropylsulfonyl-2-furyl) 2(alpha,alphadichloroacetamido) -1 ,3 -propanediol 1-(5-n-butylsulfonyl-2furyl) 2 (alpha,alphadichloroacetamido -l 3 -propanedioll-(5-methylsulfonyl-2 furyl 2 acetamido 1,3 propanedioll-(5-methylsulfonyl-2 furyl) 2 (alpha chloroacetamido) -1,3-propanediol1-(S-methylsulfonyl-Z-furyl) 2 (alpha bromoacetamido)-1,3-propanedio1l-(S-methylsulfonyl-Z furyl) 2 (alpha,alphadibromoacetamido)-1,3-propanediol l-(S-methylsulfonyl-Z-furyl)-2 (alphamethylsulfonylacetamido) -l ,3 -propanediol Thealkylsulfonylfurylamidopropanediols of the invention can be preparedfrom previously known organic compounds by a novel synthetic route whichI have discovered. A number of new intermediate organic compounds areinvolved in the steps of this synthesis.

Certain of these new intermediate compounds and all of the compoundsrepresented by Formula 1 may exist in optical isomeric form.Stereoisomeric forms as used herein refer to the spatial arrangement ofthe polar groups on the two asymmetric carbon atomswith reference toerythrose and threose. To differentiate between these two possible formsthe convention will be employed herein which designates thediastereoisomeric pair related to erythrose in configuration as theerythro form, and the diastereoisomeric pair related to threose as thethreo form.

To further designate the threo form of the compounds of this invention,I have designated as the threo form the major product obtained from thealuminum isopro- 2,719,854 Patented Oct. 4, 1955 poxide isopropanolreduction of ketones having the formula I o ITTH Acyl RSO: -lionomorrwhere R has the same significance as in Formula 1.

Both the threo and erythro forms exist as racemates of optically activedextro (d) and levo (l) rotatory isomers as well as in the form of theindividual or separated dextro (d) and levo (l) optical isomers.

In view of the difliculty of representing the variousoptical isomerswith plane formulas, I have used the customary structural formulas andadopted the following convention in order to designate the opticalconfiguration, and appropriate notation is used under. the formula, forexample, (l)-threo form, (d)-threo form, (l)-erythro form, (d)-erythroform and (dl) -threo form and the like.

solved mixture of isomers but also the individual isomers and racemates.

Using the above conventions, a method for the production of thealkylsulfonylfurylamidopropanediols of the invention can bediagrammatically represented as follows:

p 0 Br 0 Ji-ou.

Step 1 RSK O lam.

0 li-GH,

HOAcl Br;

Step 2 Step 3 Step 4 I CHt-N -o orn RSO 0 CHaN-CH2-N\ CH: Br

Step 5 l ll RS01 U CCH2NHCH2OSO2H Step 6 ll i O RSbFUiECiHrNTL-HGI Step7 l Acylation rroiro Weak- Base reduction or Na'BHf WIie'i'e R andacylHave the same significance as in' Fer-none 11* step 1} array" process,which involves preparing a" methyl QS-a'lIYlirierEaptG Q-ffiryl)ke'to'neby reacting Z-a'cet'yl-S- bromofurane with an alkali metal alkylmefcaptiiie, such as potassium alkyl mercaptid'e; ina liquid alcoholicmedium, ie-fully" described and claimed in m-y joint copon'diiigapplication with Walter A-'-. Gregery',-Seria1 No. 298,843, filed July14, 1952.

The ketone produced in step" 1" is oxidized using hydrogen peroxide andglacial acetic acid to yield a methyl- (S-alkylsulfonyl-2furyl) kerone.

Step 3 comprises brominating the methyl(5-alkyl-sulfonyl-Z-furyl) ketoneof Step 2 to produce a bromomethyl (S-alkylsulfonyl-Z-furyl) ketorielThis is preferably er: fected by the dropwise addition of liquid bromineto a glacial acetic acid solution of the ketone resulting from Step 2. p

In Step 4 of the prceess'drnie invention, the bromomethyl(S-alkylsulfonyl-Z-furyl) ketone of Step 3 is mixed in a liquid medium,such as, for example, ethylidene di; chloride, with hexamettiylenetetramine to obtain N 6- alkylsulfonyl-2furoylmethyl)hexamethylenetetraminiurn bromide.

The tetraminium salt produced in accordance with Step 4 is convertedto'(hydioxymetliylainino)methyl 5- alkylsulfonyl-Z-furyl) ketone sulfiteusing sulfur dioxide and water as shown on the above diagram as Step 5.In some instances it may be found" preferably to proceed directly to thesulfite without isolation of the hexamethylenetetraminium halide. U

The sulfite of Step 5 is rbadily converted into N-(S-a1kylsulfonyl-2-furoyl methylamin hydrochloride using hydrochloric acid.It is preferred to carry out this conver sion of sulfite to aminehydrochloride (Step 6) in the presence of an alcohol such as absoluteethanol.

Step 7 comprises N-acylating the amine hydrochloride of Step 6. Theacylatiorr preferably effected usiii'g dichloroacetyl chloride or asimilar acidhalide;

The arflide derivative produced in accordance with Step 7 of myprocessis subjected foa'ii aldol type'of condensation to yield a compound ofthe formula This condensation is preferably carried out in an alcoholicmedium such as, for example, ethanol or, methanol, using sodiumbicarbonate or potassium carbonate, and an aqueous formaldehyde of36-38% concentration.

Step 9, the final step in the process of the invention, involves areduction of the carbonyl group of the compound produced in Step 8 to ahy'droxyl group. This reduction can be effected in good yields by using.either of two} rrietliod'si v one method involves the use" of's'odiim'i'Horoliydride, NaBI-Ln- It is preferred to carry out the reductionus'in'g NaBHii-in th'e'pr'e'sence-of an alcohol suchfor instance,methanol or ethanol. This method-yieldsarmature of (a'l)-threo and(dl)-erythro forms of the alkylsulfonylfurylamid'opropanediolsi oftheinvention.

The alternative method of Step g is referred to as theMeerwein-Ponndorf-Verly reductiont- This reduction method is describedby A. L. Wilds on page 205 of chapter 5 of Organic Reactions, volume 2,-John Wiley & Sons, Inc., N. Y. (1944-) This: method of reduction givesm'a'in- 1y (dl)-threo form of the 1-(S-alkylsulfonyl-Z-furyl)-2-amido-l'j-propanediols of the invention;

The compounds of the present invention a're useful-as drugs for thecontrol of bacterial and rickettsial infections.

* They are also of use in viral and fungal infections. The" compoundsfind further useas antibacterial agents and in the control of growth ofmicfoorganisms such as, for example, yeast and fungi.

In order to better understand the invention reference should be had tothe following illustrative examples. Partsgiven are by weight unlessotherwise specified.

Example 1 Preparation of dl)-threo 1 5 -methylsulfonyl i-fixryl') 2-alpha,alpha-dichloroacetamido) -1 ,3-propanediol.

d1; nae-0613011, oinso'z O om-oH-omoia and eighty-nine parts of methyl SbrOmofiIrylKetone" is theira'ddeldin in one portion.- The reaction"mixture" is refluxed for a period of three hours, cooled aridpdii'r'dintestine-pans by volume of'wat'er. The desires-precinct; methyl(5-methyl-mercapto-2-fnryljketb'rie',-- isseparated by extraction;collected, washed with water; dr'ied and dis tilled under reducedpressure. The product has the formula cuts o c'rtt A. mixtureconsistingof l3 4 parts' o'frfie'tliyl s-martyrmercapto i furyl) keto'ne, 326parts by volume of glacial (5-methylsulfonyl-Z-furyl) ketone thusobtainedis'dried and crystallized from a 1:1 benzene-hexane mixture; It

has the formula Bromomethyl (S-methylsulfonyl-Z-furyl) ketone, ms-

ne'x t step in my synthesis, is repared according-' to the followingprocedure:

Tea mixture-of: 13 1 parts of methyl- (S-rirethylsulfonyd 2-furyl)ketone and 285 parts by volume of glacial acetic acid there is added afew drops of bromine. There is a short induction period of approximatelytwenty minutes before the reaction begins. Bromine (112 parts) is addeddropwise over a period of one hour to the reaction mixture which ismaintained at a temperature of 16 C. The mixture is filtered. Theproduct is collected, washed by slurrying with 1500 parts of water,filtered, air-dried and recrystallized from benzene. The product,bromomethyl (S-methylsulfohyl-Z-furyl) ketone, has "the formula O t CHzSO O H213 r A mixture of 147 parts of bromomethyl(-methylsulfonyl-2-furyl) ketone, 77 parts of hexamethylenetetramine and700 parts by volume of ethylidene dichloride is stirred vigorously for aperiod of one hour. The product comprisingN-(5-methylsulfonyl-2-furoylmethyD- hexamethylenetetraminium bromide iscollected by filtration, washed by slurrying twice with ether andair-dried. Its formula is as follows:

CH: N

-A vigorously stirred suspension consisting of 220 parts of N (5methylsulfonyl 2 furoylmethyl)hexamethylenetetraminium bromide and 1000parts of water at a temperature of from to C. is treated with a rapidstream of sulfur dioxide for a period of two hours. The reaction mixtureis filtered and a solid is collected and dried. This solid is(hydroxymethylamino)methyl (5- methylsulfonyl-Z-furyl) ketone sulfiteand has the formula 0 CHsSOr-LO CHzNHCHzOSOaH A mixture consisting of 57parts of N-(S-rnethylsulfonyl-2-furoyl)methylamine hydrochloride and 150parts of dichloroacetyl chloride is refluxed for a period of twentyminutes. It is then cooled and filtered. The resulting alpha,alphadichloro N (5 methylsulfonyl Z-furoylmethyl) acetamide is dried andrecrystallized from ethylene dichloride. It has the formula h) 0 OHQSOPO CCH2NH CHCh A mixture consisting of 44 parts of alpha,alpha-dichloro N(5 methylsulfonyl 2 furoylmethyl)- acetamide, 17.4 parts of 36% aqueousformaldehyde, 1.7 parts of sodium bicarbonate and 450 parts by volume ofmethanol is stirred on a water-bath fora period of chloro N [2 hydroxy(5 methylsulfonyl 2 Its formula is furoyl)ethyl]acetamide, is collected.shown below:

O IYIH( BOHCI2 CHaSO o -CHCHzOH A mixture consisting of 20.6 parts ofalpha,alphadichloro N [2 hydroxy (5 methylsulfonyl 4 2furoyl)ethyl]acetamide, 12.2 parts of redistilled aluminum isopropoxideand 1000 parts by volume of isopropanol is refluxed for a period of fourhours. During this period approximately 500 parts of the solvent mixture(is'opropanol-acetone) is removed by distillation. The remainder of thesolvent is removed by distillation under reduced pressure. A yellowsolid residue which remains is cooled and treated with 200 parts byvolume of 2. N hydrochloric acid. The acid-treated residue which is (dl)threo 1 (5 methylsulfonyl 2 furyl) 2 (alpha,alpha-dichloroacetamido)'1,3 propanediol is recrystallized from ethyl acetate. This end producthas the formula n: 1711100011011 CHaSO 6 CH-CHCH2OH (db-three form"Example 2 Preparation of (dl)-thre0-1-(5-ethylsulfonyl-2-furyl)2-(alpha,alpha-dichloroacetamido) -1,3-propanedio1 on l wnooonoh C2H5SOO CH-CHCH2OH uct consisting substantially of methyl (5-ethylmercapto-Z-furyl) ketone is extracted with a solvent, washed, dried and distilledunderreduced pressure. The product has the formula p 0 .CZH5S O -CH:

A mixture consisting of 151.3 parts of methyl (5-ethylmercapto-Z-furyl)ketone, 340 parts by volume of glacial acetic acid and 425 parts byvolume of 30%hydrogen peroxide is heated on a steam bath for a period oftwo hours. It is then cooled in an ice bath neutralized and Icontinuously extracted with benzene 'over a 24 hour period. The benzeneis removed from the extract by distillation. The product which remainsis methyl (5- ethylsulfonyl-Z-furyl) ketone. This product is then dried.Its formula is as follows: i i

A mixture consisting of 153.5 parts of methyl (5-ethylsulfonyl-2-furyl)ketone and 300 parts by volume of glacial acetic acid is treated with afew drops of bromine.

After a short induction period reaction begins. 'One hundred andtwenty-one parts of bromine is then added.

drdpviiiseover a" period] of one hour to the reaction mix tu'rwhich ismaintained at-a' temperature of F6 G} Themixture is stirred for anadditional hou ig spa'rged with dry nitrogen for one hour and filteredlThe resulting" product; broinometliyl (5-ethylsulfonyl=2 fiirylD"ketone',-

is' collected; washed by slurrying twice with 1500 parts of water,filtered, dried and recrystallized from benieifet- The product has theformula A mixture consisting of I63 ans'o'fb'ro omettiyl (5ethylsulfonyl-Zfuryl) ketone, 85.8 parts" of lie'xarnethylenetetramineand 800 parts by'voliime of eth'yliden'e dichloride is vigorouslystirred for a period of one hour. The resulting. N(5-ethylsulfonyl-2-furoylmethyDhexamethylenetetraminiumbromide iscollected by filtration; washed twice'with' 500 m1. of ether andair-dried. This bromide hastlie formula C-Hz N U l creaseso "-cmsf-c'mnf em Bi ,i u CH2-N A vigorously stirred suspension consisting of 223parts of N (5 ethylisulfohyl" 2" furoylmethynhexamethylenetetraminiumbrotnide' and 750 parts of. Water at a temperature of from 10 to C. istreated with a rapid stream of sulfur dioxide over a two hour period.The product which is collected by filtration and dried consists of(hydroxymethylamino)methyl (5 ethylsulfonyl 2 rum keto'n'e" sulfite. Thesulfi'te has the" formula 0 I mmsmUh-onmnbmosom A mixture consisting of112 parts ofihydroxymethylaminoY-rnethyl' ("S-ethylsulfonyl-Z-furjil)ket'o'ne' sulfite,

140 parts by volume of concentrated hydrochloric acid and 280 parts byvolumeof absolute ethanol is refluxed for a p'eriodof one houri Thereaction mixture is' re'-' duced in" volume to approximately 75' partsby' volume by distillation under reduced pressure and is then cooled".The resulting product, N'-('5-ethyISuIion l-Z-furoyl)m'eth ylar'ninehydrochloride; is collected by filtration, washed with a' lz'l' mixtureof absolute" ethanol and ether and dried thorou hly at a" temperature of60 c; in a vacuum oven. The product has the formula Kn ixture consistingof 607 parts OfN-(Sj-thYlSlilfonyl 2 fiiroyl)methylatnine hydrochloride,100' parts of dichloroacetyl chloride and 400' parts by volume ofbenzene is refluxed'tbr" aperiod of eighteen hours; It isthen coole'difilter'e'd and the alpha,alpha dichlo'ro-N-(5ethylsulfonyl-l-fnroylmethyl)acetamide thus produced is collected. It'is washed with benzene, then with ether and recrysfali'z'ed fromethylene dichloride. The substi-' tuted acetamide' has the formula Amixture consisting of 39.4 parts of alpha,alpha-dichloro N t 5ethylsulfonyl-2 furoylmethyl) acetamid'e, 1-5

partsof 36% aqueous formaldehyde, 1.5 partsof sodium bicarbonate and250' parts" by volume of methanol is stirred for a? period of two hourswhilethe tiemprat of the'mixture ismaintained at 40-45 C.- The mixture 8is then cooled in an ice bath and filteredi Theresulting alphagalphadichlbrd- N [2f hydrant- (5' ethyl sulfonyl 2 fu-royl )ethyl-]-acetamidehasthe" formula- A- mixturei consisting of" 17-.1 parts of.alphmalph'ari dichloro -"N -[2---'hydroxy (5 ethyl'sulfonyla-l furoylyethyll-acetamide, 10.2 parts of redistilled aluminiumisopropoxide and450 parts by volume of isopropanol is refluxed for a period-"01- fourhours. During this period about 225 par-ts by volumeof: the solventmixture (isopropanol-acetone) is removed by distillation. The remainderof thesolventismemoved underreduced'pressure-to give a yellow residue;Thisis-cooled and treated with 1 25 parts by volume of- 2 Nhydrochloric: acid.

The: acid-treated material, which is the desired (dl)g three 1 (5ethylsulfonyl 2-- fury-l)-2-(alpha,a1pha dichloroacetamidofi-1,3-propanediol,, is collected: byfiltra- This final tion' andrecrystallized from ethyl acetate; product has the formula 0 (H1 ITIHK-JCHCH onaiso ononorrion (dU-thr'eo form Eic'ampleS Preparation of: (dithreo=k-i-n propylsulfonylflfurylyll- (.alpl'laalpha-dibhliaroanetarnido)?-1,3-prt p2ine= diol l g err. embodimenseamenO Y en cncnion Methyl! (5 --n propylmercapto 2.- furyl) ketonenthestarting material in this preparation, is produced accord-i ing to thefollowing method:

To a solution of 73.7 parts of potassium hydroxide in 1000 parts volumeof absolute ethanol at 25 C. there is added 8316 parts of n-propylmercaptan-s Methyl (-S-bromo-Z-furyl) ketone (189' parts) is addedinoneportion and the mixture is refluxed for a periodof three hours. Themixture is then cooled and poured into 3000 parts of water. Theresultingproduct is: separated by extraction with ben-zene, 'collected,dried and. distilled under reduced pressure; It.

-' has. the formula n-CsHrho d-OCH:-

A mixture consisting of 144.7 parts of methyl (5-11-propylsulfonyl-Z-friryll): ketone and 22-5 parts by volume of glacialacetic acid is treated with a few drops of bromine; A ri inductionperiod of approximately" twenty minutes: elapses before the reactionbegins. (107.2 parts) is added dropwise over a period; of: one; hour tothe reaction mixture, whose temperature. is:

Bromine? maintained at 16 C. The reaction mixture is stirred for anadditional period of one hour, sparged with dry nitrogen and filtered. Aproduct comprising bromomethyl (S-n-propylsulfonyl-Z-furyl) ketone iscollected, washed twice with 1500 parts of water, filtered, collected,dried and recrystallized from benzene. The product has the formula lln-oamsow iloomnr A mixture consisting of 153.4 parts of bromomethyl(S-n-propylsulfonyl-Z-furyl) ketone, 72.8 parts ofhexamethylenetetramine and 700 parts by volume of ethylidene dichlorideis stirred vigorously for a period of one hour. The product which isobtained is N-(S-n-propylsulfonyl 2furoylmethyl)hexamethylenetetraminium bromide. It is collected byfiltration, washed twice with 500 parts by volume of ether and dried.The bromide has the formula CH2-N CH: CH N A vigorously stirredsuspension consisting of 217 parts of N npropylsulfonyl-Z-furoylmethyl)hexamethylenetetraminium bromide and 1000parts of water at a temperature of from to C. is treated with a rapidstream of sulfur dioxide for a period of two hours. The resulting(hydroxymethylamino)methyl (S-n-propylsulfonyl-Z-furyl) ketone sulfiteis collected by filtration and dried. It has the formula 0 n-CgHrSOr-Ui)OHzNHCHzOSOzH A mixture consisting of 113.8 parts of(hydroxymethylamino)methyl (5 n propylsulfonyl-Z-furyl) ketone sulfite,125 parts by volume of concentrated hydrochloric acid and 250 parts byvolume of absolute ethanol is refluxed for a period of two hours. Thereaction mixture is concentrated to approximately 100 parts by volume bydistillation under reduced pressure and is then cooled. The desiredproduct, N-(S-n-propyl-Z- furoyl)methylamine hydrochloride, is collectedby filtration, washed with a 1:1 mixture of absolute ethanol and etherand dried thoroughly at a temperature of 60 C. in a vacuum oven. Theproduct has the formula 0 n-CaHz-SOU CH2NHz-HC1 A mixture consisting of58.7 parts of N-(S-n-propylsulfonyl-Z-furoyl)methylamine hydrochloride,100 parts of dichloroacetyl chloride and 500 parts by volume of drybenzene is refluxed for a period of eighteen hours, then cooled andfiltered. The resulting product is collected, washed with benzene, thenwith ether and recrystallized from ethylene dichloride. The product,alpha,alpha-dichloro-N-(5-n-propylsulfonyl 2 furoylmethyl)acetamide, hasthe formula O O t t n-CaH'lS O o CHzNH CHCI:

A mixture consisting of 37.6 parts ofalpha-alphadichloro-N-(5-n-propylsulfonyl 2 furoylmethyl(acetamide, 13.3parts of 36% aqueous formaldehyde, 1.3 parts of sodium bicarbonate and250 parts by volume of methanol is stirred at a temperature of from 40to 45 C. for a period of two hours, cooled in an ice-bath and 10filtered. The

the formula 0 0 1%IHC-CHO1: n-CaH1SO O ii-CH-CHzOH A mixture consistingof 18.6 parts of alpha,alphadichloro-N [2hydroxy-S-n-propylsulfonyl-2-furoyl)- ethylJ-acetamide, 10.2 parts ofredistilled aluminum isopropoxide and 350 parts by volume of isopropanolis refluxed for a period of four hours. During this period about 175-parts by volume of the solvent mixture (isopropanol-acetone) is removedby distillation. The

remainder of the solvent is removed by distillation under reducedpressure to yield a yellow residue. The residue which comprises fonyl 2furyl) 2 a (alpha,alpha-dichloracetamido)- 1,3-propanediol is cooled andtreated with parts of 2 N-hydrochloric acid. The product is furtherpurified by crystallizing it from ethyl acetate. The product' has theformula n q i f o i (')H nniicuol, n-C:H1SO o on-cn-ornorr (dl)-threeform Example 4 Preparation of (dl) furyl) 2(alpha,alpha-dichloracetamido)- 1,3 propanediol.

on; nn nnooorron onsor-L oH-oHomoH 0 To a solution of 73.7 parts ofpotassium hydroxide in 1000 parts of absolute ethanol at 25 C.

there is added 83.6 parts of isopropyl mercaptan. One

hundred and eighty-nine parts of methyl (5-bromo-2- furyl) ketone isnext added in one portion. The resulting mixture is refluxed for aperiod of three hours, cooled and poured into 3000 partsof water.The'desired methyl (5-isopropylmercapto-2-furyl) ketone is' separated byextraction, dried and distilled under re-' duced pressure. This ketonehas the formula (13H: O HC-S -iiCHz l 0 A mixture consisting of 136.1parts of methyl (5- isopropylsulfonyl-2-furyl) ketone and 225 parts byvolume of glacial acetic acid is treated with a few drops of bromine.After an induction period of about twenty minutes, the reaction begins.Bromine (100.8 parts) is added dropwise over a period of one hour to thereaction mixture which is maintained at a temperature of 16 C.

resultingalpha,alpha-dichloro-N-[2-hydroxy-(5-n-propylsulfonyl-2-furoyl)ethyl]acetamide has- (dl -threo-1- S-n-propylsul- I threo 1(5-isopropylsulfonyl 2- The mixture! is: stirred for ani additional:hourand sp'arged' with nitr o'ge'n'-.t The bromomethylzS'-isopropylsu1'- fonyl-2-furyl) ketone so produced is coilectedxbyfiltrw tion and washed twice with 1200 parts of water, dried andrecrystallized from'i benzene:.- This ketone has the formula A mixtureconsisting" of 13856 parts of- 'bromom'etliyl (S isopropylsulfonylEZ-furyl) ketone; 65 i9 parts of Berra-- metliylenetetraniine and700partsb'y volume of ethyl id'e'n'e dichlorideis stirred vigorously fora period ofone hour: The resulting N (S' i'soprGpylSuIfonyl -2-fur'oylmetiryl)hexamethylenetetraminium bromide is collectedhyfil'tration', washed twice with 500 parts by vol umeof ether anddried. Thehromide has the formula A vigorously stirred'suspensihn.consistihg of 196 parts of N (5 isopropylsulfonyl 2furylmethyl)hexamethylenetetraminum bromide and 800" parts of water at atemperature of to C. is treated with a rapid stream of suliun dioxidefor. a periodv of two" hours. A. solid consisting of(hydroxymethylamino)methyl (5-is0propylsulfonyl-Z-furyl) ketone sulfiteis collected by filtration and dried. The sulfite has the formula CfiaAmixtureconsisting of 48.1 parts. of N-(S-isopropYlsulfonyhZ-EurOyDmethyIamine; hydrochloride, 100 parts ofidichlonoacetyll chloride and500 parts. by volume of dry benzene, is refluxed for a period. of,eighteen hours, cooled, and. filtered. The resulting.alpha,alpha-dichloro.- N-(5 isopropylsulfonyl-2-furoylmethyljacetamideis collected and washed with parts ofibenzene, then with. ether andrecrystallized from ethylene dichloride. This; substituted acetamide hasthe formula A mixture consisting of 28.1 parts of alpha-,alpha-dichloroN'- (Seisopropylsulfionyl l-furoylmethyl)acetam ide; 1.0 .0. parts-M3692: aqueous formaldehyde, 110 part: of sodium bicarhonate? and200-p'arts by volume ofi met-1r anol is stirred atatemperature-ofi4045ffor-'a zperiod of three hours-cooled: in an iceabath and filtered"Theproduct obtained; aI hmaIpha-diChlQrO-N-E2-hydroxy (5--isopropylsulfonyli-furoyl) ethyl] acetamide; has the for- H5 \CHSO mula:

o ixoiter, 0 ii-iinomon. OH;

A mixture consisting of 13.4 parts of alpha,alphadichloro N [2 hydrozsy('5 --isopropylsulfonyl 2- furoyl)ethyl]acetamide, 7.3 parts ofredistilled aluminum isopropoxideand 300partsby volume of isopropanol-isrefluxed 'for a period of 'four hours;

ture' (-isopropanol -acetone') is removed by distillation:

The remainder of the solvent is removed by distillation under reducedpressure to give ayellow residue contain-- ing (til)-threo-1-(5-isopropylsulfonyl-Z-furyl) 2 ('al'plia;

al'phwdi'chloroacetamido)-1,3 propanediol. The residue is cooled andtreated with parts of 2 N h'ydrochlorieacid and finallyrecrystallizedfrom ethyl acetate. The product has the. formula Example '5 Preparationof (a'l) -threo-1-(5amethylsulfonyl 2-funyll- 2-(alpha,alpha-dibromoacetamido).-1,3-propanediol.

O: l l (fH' ITIHiiCH-Bn CHsSO CH CHCHQOH A mixture consisting of60"parts of N-(S-methylsulfonyl-Z-iuroyl)methylamine hydrochlorideprepared as in Example" 1, 118 parts of dibromoacetyl chloride, and 300parts by volume of toluene is refluxed for a period of' five hours, thencooled and finally filtered; The product" obtained isalpha,alpha-dibromo-N-(S-methylsulfonyl-L furoylmethyl'.)acetamide; Itis washed with benzene, then ether and dried. The product has theformula 0 0 ii i 011350.: .0 CHzNH CEBU.

A mixture. consisting of; 40.3 parts of alpha,alpha-di bromo-N-(5rnethylsulfonyl'- 2 furoylmethynacetamide, 12.5 parts of 36%aqueousformaldehyde, 1.3 parts of sodium bicarbonate and 225 parts} byvolume of methanol is stirred at atemperature 0t 4045 C. for a period oftwo hours, cooled and filtered. A solid comprising alpha,a 1pha dib'romoN [2- hydroxy- (5 methylsulfonyl 2-furoyl') ethyl] a'cet'amide iscollected and dried; The product has the formula ,bromo N [2 hydroxy (5methylsulfonyl 2 furoyl)ethyll acetamide, 7.1 pa rts of redistilledaluminum isopropoxide and' 300' parts: by volume-of. isopropanol isrefluxed for a period of four hours. During this period about partsr by'volume: of the solvent: mixture (isopropanoh-acetOue): isremoved bydistillation. The. reamaindenqof-thm solvent; is removed by distillationtmderr reduced-pressure'to yield. a yellow residue. which ispreadbminamtly (idly-thread -(5+methylsulfonyl=2furyl:)i-2-(ahi phaalpha dibromoacetamido);-'1,3--:pnopanediol.. It is.

During this period v approximately 150 parts 'by volume of the solvent Amixture consistingof- 15 .2 partsof alpha,alpha-di 13 cooled and treatedwith 70 parts of 2 N hydrochloric acid and recrystallized from ethylacetate. The product has the formula OH lTIHCOCHBrz GHaSOz- CH-CHCHzOH(dl)-threo form I claim: 1. A compound of the formula (|)H lTIH-Acyl RSO0 CH-OH-CHiOH where R is a lower alkyl radical and acyl is a member ofthe group consisting of acetyl, chloroacetyl, brornoacetyl,dichloroacetyl, dibromoacetyl and alpha-methylsulfonylacetyl radicals.

2. (dl) Threo 1 methylsulfonyl 2 furyl)- 2 (alpha,alphadichloroacetamido) 1,3 propanediol.

3. (dl) Threo 1 (5 ethylsulfonyl 2 furyl)- 2 (alpha,alphadichloroacetamido) 1,3 propanediol.

4. (dl) Thrco 1 (5 n propylsulfonyl 2 furyl)- 2 (alpha,alphadichloroacetamido) 1,3 propanediol.

5. (dl) Threo l (5 isopropylsulfonyl 2 furyl)- 2 (alpha,alphadichloroacetamido) 1,3 propanediol.

6. (dl) Threo l (5 methylsulfonyl 2 furyl)- 2 (alpha,alphadibromoacetamido) 1,3 propanediol. 7. In a process for preparing acompound of claim 1, the steps comprising oxidizing a compound of theformula I R-S (BCH:

where R is a lower alkyl radical with hydrogen peroxide and glacialacetic acid to obtain a compound of the formula 0 a R S i3CHsbrominating the latter compound, recovering a compound of the formulahydrolyzing the latter compound with hydrochloric acid to obtain ahydrochloride of the formula 0 ll R S CHzNHrHCl acylating the lattercompound, recovering a compound of the formula 0 R UiicH NH Acyl 0 (I)NH-Acyl R (S) O H-CH2OH reacting the latter compound with a member ofthe group consisting of aluminum isopropoxide and sodium borohydride,and recovering a compound of the formula 8. In a process for obtaining(dl)-threo-l-(S-methylsulfonyl 2 furyl) 2 (alpha,alphadichloroacetamido)-1,3-propanediol, the steps comprising reacting methyl(S-methylmercapto-Z-furyl) ketone with hydrogen peroxide in the presenceof glacial acetic acid, recovering methyl (5-n1ethylsulfonyl-2-furyl)ketone thus formed, brominating the latter compound with liquid brominein the presence of glacial acetic acid to obtain bromomethyl(S-methylsulfonyl-Z-furyl) ketone, reacting the latter compound withhexamethylenetetramine to obtain N- (5 methylsulfonyl 2furoylmethyl)hexamethylenetetramine bromide, reacting the lattercompound so obtained with sulfur dioxide and water, recovering(hydroxymethylamino)methyl (S-methylsulfonyl-Z-furyl) ketone sulfite,reacting the latter compound so obtained with hydrochloric acid,recovering N-(S-methylsulfonyl- 2-furoyl)methylamine hydrochloride,reacting the latter compound with dichloroacetyl chloride to obtainalpha, alpha dichloro N (5 rnethylsulfonyl 2 furoylmethyl)-acetamide,reacting the latter compound so obtained with aqueous formaldehyde in adilute alkaline solution, recovering alpha,alpha dichloro N [2- hydroxy(5 methylsulfonyl 2 furoyl)ethyl]acetamide, reducing the latter compoundwith aluminum isopropoxide in the presence of isopropyl alcohol, andrecovering (dl) threo 1 (5 methylsulfonyl 2 furyl)- 2 alpha,alphadichloroametamido) 1,3 propanediol.

References Cited in the file of this patent UNITED STATES PATENTS2,515,241 Long July 18, 1950 2,547,712 Long Apr. 3, 1951 2,562,107 LongJuly 24, 1951 FOREIGN PATENTS 512,433 Belgium July 15, 1952 828,549Germany Jan. 17, 1952 OTHER REFERENCES Keskin et al., J. Org. Chem.,vol. 16, No. 9, pp. 1333- 36, 1951.

Cutler et al., J. A. C. S. 74, pp. 5475-81 (received June 2, 1952).

1. A COMPOUND OF THE FORMULA 